Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9OBWPH)

• DOT Name: Signal transducing adapter molecule 2 (STAM2)
• Synonyms: STAM-2; Hrs-binding protein
• Gene Name: STAM2
• Related Disease:
  Non-insulin dependent diabetes
  Abscess
  Alzheimer disease
  Bacterial meningitis
  Breast cancer
  Chronic obstructive pulmonary disease
  Congestive heart failure
  Diabetic kidney disease
  Fatty liver disease
  Intrahepatic cholangiocarcinoma
  Neoplasm
  Bacterial infection
  Hepatocellular carcinoma
  Prostate cancer
• UniProt ID: STAM2_HUMAN
• PDB ID: 1X2Q; 1X5B; 2L0T; 5CRV; 5IXF
• Pfam ID: PF00018 ; PF02809 ; PF00790
• Sequence:
  MPLFTANPFEQDVEKATNEYNTTEDWSLIMDICDKVGSTPNGAKDCLKAIMKRVNHKVPH
  VALQALTLLGACVANCGKIFHLEVCSRDFATEVRAVIKNKAHPKVCEKLKSLMVEWSEEF
  QKDPQFSLISATIKSMKEEGITFPPAGSQTVSAAAKNGTSSNKNKEDEDIAKAIELSLQE
  QKQQHTETKSLYPSSEIQLNNKVARKVRALYDFEAVEDNELTFKHGEIIIVLDDSDANWW
  KGENHRGIGLFPSNFVTTNLNIETEAAAVDKLNVIDDDVEEIKKSEPEPVYIDEDKMDRA
  LQVLQSIDPTDSKPDSQDLLDLEDICQQMGPMIDEKLEEIDRKHSELSELNVKVLEALEL
  YNKLVNEAPVYSVYSKLHPPAHYPPASSGVPMQTYPVQSHGGNYMGQSIHQVTVAQSYSL
  GPDQIGPLRSLPPNVNSSVTAQPAQTSYLSTGQDTVSNPTYMNQNSNLQSATGTTAYTQQ
  MGMSVDMSSYQNTTSNLPQLAGFPVTVPAHPVAQQHTNYHQQPLL
• Function: Involved in intracellular signal transduction mediated by cytokines and growth factors. Upon IL-2 and GM-CSL stimulation, it plays a role in signaling leading to DNA synthesis and MYC induction. May also play a role in T-cell development. Involved in down-regulation of receptor tyrosine kinase via multivesicular body (MVBs) when complexed with HGS (ESCRT-0 complex). The ESCRT-0 complex binds ubiquitin and acts as a sorting machinery that recognizes ubiquitinated receptors and transfers them to further sequential lysosomal sorting/trafficking processes.
• Tissue Specificity: Ubiquitously expressed.
• KEGG Pathway:
  Endocytosis (hsa04144)
  JAK-STAT sig.ling pathway (hsa04630)
• Reactome Pathway:
  Ub-specific processing proteases (R-HSA-5689880)
  Negative regulation of MET activity (R-HSA-6807004)
  Cargo recognition for clathrin-mediated endocytosis (R-HSA-8856825)
  Clathrin-mediated endocytosis (R-HSA-8856828)
  InlB-mediated entry of Listeria monocytogenes into host cell (R-HSA-8875360)
  RHOU GTPase cycle (R-HSA-9013420)
  Endosomal Sorting Complex Required For Transport (ESCRT) (R-HSA-917729)
  EGFR downregulation (R-HSA-182971)

Molecular Interaction Atlas (MIA) of This DOT

14 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Non-insulin dependent diabetes	DISK1O5Z	Definitive	Biomarker	[1]
Abscess	DISAP982	Strong	Biomarker	[2]
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[3]
Bacterial meningitis	DISRP9SL	Strong	Altered Expression	[4]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[5]
Chronic obstructive pulmonary disease	DISQCIRF	Strong	Biomarker	[6]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[6]
Diabetic kidney disease	DISJMWEY	Strong	Biomarker	[7]
Fatty liver disease	DIS485QZ	Strong	Biomarker	[8]
Intrahepatic cholangiocarcinoma	DIS6GOC8	Strong	Biomarker	[9]
Neoplasm	DISZKGEW	Strong	Altered Expression	[10]
Bacterial infection	DIS5QJ9S	moderate	Biomarker	[11]
Hepatocellular carcinoma	DIS0J828	moderate	Biomarker	[12]
Prostate cancer	DISF190Y	moderate	Altered Expression	[13]

14 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Signal transducing adapter molecule 2 (STAM2).	[14]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Signal transducing adapter molecule 2 (STAM2).	[15]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Signal transducing adapter molecule 2 (STAM2).	[16]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Signal transducing adapter molecule 2 (STAM2).	[17]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Signal transducing adapter molecule 2 (STAM2).	[18]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Signal transducing adapter molecule 2 (STAM2).	[19]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Signal transducing adapter molecule 2 (STAM2).	[20]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Signal transducing adapter molecule 2 (STAM2).	[21]
Lindane	DMB8CNL	Approved	Lindane increases the expression of Signal transducing adapter molecule 2 (STAM2).	[19]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Signal transducing adapter molecule 2 (STAM2).	[22]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Signal transducing adapter molecule 2 (STAM2).	[23]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Signal transducing adapter molecule 2 (STAM2).	[24]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Signal transducing adapter molecule 2 (STAM2).	[25]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Signal transducing adapter molecule 2 (STAM2).	[19]

References

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• [2] Escherichia coli hemoglobin protease autotransporter contributes to synergistic abscess formation and heme-dependent growth of Bacteroides fragilis.Infect Immun. 2002 Jan;70(1):5-10. doi: 10.1128/IAI.70.1.5-10.2002.
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• [4] Accuracy of heparin binding protein: as a new marker in prediction of acute bacterial meningitis.Braz J Microbiol. 2018 Nov;49 Suppl 1(Suppl 1):213-219. doi: 10.1016/j.bjm.2018.05.007. Epub 2018 Aug 17.
• [5] Enhanced hexosamine metabolism drives metabolic and signaling networks involving hyaluronan production and O-GlcNAcylation to exacerbate breast cancer.Cell Death Dis. 2019 Oct 23;10(11):803. doi: 10.1038/s41419-019-2034-y.
• [6] Home-based telerehabilitation in older patients with chronic obstructive pulmonary disease and heart failure: a randomised controlled trial.Age Ageing. 2018 Jan 1;47(1):82-88. doi: 10.1093/ageing/afx146.
• [7] Maximum morning home systolic blood pressure is an indicator of the development of diabetic nephropathy: The KAMOGAWA-HBP study.J Diabetes Investig. 2019 Nov;10(6):1543-1549. doi: 10.1111/jdi.13040. Epub 2019 May 7.
• [8] Iso- or hyperintensity of hepatocellular adenomas on hepatobiliary phase does not always correspond to hepatospecific contrast-agent uptake: importance for tumor subtyping.Eur Radiol. 2019 Jul;29(7):3791-3801. doi: 10.1007/s00330-019-06150-7. Epub 2019 Apr 1.
• [9] Differentiation between inflammatory myofibroblastic tumor and cholangiocarcinoma manifesting as target appearance on gadoxetic acid-enhanced MRI.Abdom Radiol (NY). 2019 Apr;44(4):1395-1406. doi: 10.1007/s00261-018-1847-y.
• [10] Revealing genome-wide mRNA and microRNA expression patterns in leukemic cells highlighted "hsa-miR-2278" as a tumor suppressor for regain of chemotherapeutic imatinib response due to targeting STAT5A.Tumour Biol. 2015 Sep;36(10):7915-27. doi: 10.1007/s13277-015-3509-9. Epub 2015 May 8.
• [11] Heparin-binding protein: a key player in the pathophysiology of organ dysfunction in sepsis.J Intern Med. 2017 Jun;281(6):562-574. doi: 10.1111/joim.12604. Epub 2017 Mar 28.
• [12] LI-RADS v2014 categorization of hepatocellular carcinoma: Intraindividual comparison between gadopentetate dimeglumine-enhanced MRI and gadoxetic acid-enhanced MRI.Eur Radiol. 2019 Jan;29(1):401-410. doi: 10.1007/s00330-018-5559-z. Epub 2018 Jun 19.
• [13] O-GlcNAc transferase integrates metabolic pathways to regulate the stability of c-MYC in human prostate cancer cells.Cancer Res. 2013 Aug 15;73(16):5277-87. doi: 10.1158/0008-5472.CAN-13-0549. Epub 2013 May 29.
• [14] Design principles of concentration-dependent transcriptome deviations in drug-exposed differentiating stem cells. Chem Res Toxicol. 2014 Mar 17;27(3):408-20.
• [15] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [16] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [17] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [18] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [19] Transcriptome-based functional classifiers for direct immunotoxicity. Arch Toxicol. 2014 Mar;88(3):673-89.
• [20] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [21] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [22] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [23] New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
• [24] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [25] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.